Support is requested for a Keystone Symposia meeting entitled Biology of Sirtuins, organized by Raul Mostoslavsky, Shin-ichiro Imai, Marcia C. Haigis, Eric M. Verdin. The meeting will be held in Santa Fe, New Mexico from March 8-12, 2015. Sirtuins are a unique class of NAD+-dependent enzymes that modify diverse protein substrates and serve as key regulators of critical biological processes. They target a wide range of cellular proteins in nucleus, cytoplasm, and mitochondria for post-translational modification by acetylation or ADP-ribosylation. Importantly, Sirtuins regulate responses to stress and ensure that damaged DNA is not propagated, thereby reducing the accumulation of mutations. There is considerable global interest in sirtuin biology as it is becoming recognized that they are important targets for preventive and therapeutic interventions against a variety of human pathologies, such as diabetes, cancer, cardiovascular dysfunction and neurodegenerative disease. The first Keystone Symposia meeting on sirtuin biology, Sirtuins in Metabolism, Aging and Disease (2012) focused on the emerging functions of these important molecules and was a great success with significant positive feedback from attendees. The 2015 Keystone Symposia conference on sirtuin biology will build on that earlier meeting by focusing on the integrative aspects of diverse sirtuin functions. The meeting will feature eight interdisciplinary sessions and one workshop and provide a forum where the significance of the integrative biology of sirtuins will be fully discussed and interdisciplinary interactions will be stimulated among researchers from many different fields. In this regard, this second Keystone Symposia meeting on Biology of Sirtuins will attract more diverse scientists from all over the world. The general topic of this meeting is highly relevant to the NIA mission. Although discovered originally as transcriptional silencers, sirtuins as a research field exploded following the discovery that these proteins could be a role in organismal lifespan in multiple species. Since the first discovery in yeast almost 15 years ago, the National Institute of Aging has been playing a pivotal role in supporting grants to fund research related to sirtuin biology.